Method for a gas chromatograph to mass spectrometer interface

ABSTRACT

A method of operating a gas chromatograph-mass spectrometer (GC-MS) comprising a GC column for separating analytes of a sample, a GC oven and a mass spectrometer comprises: providing a conduit extending between the GC oven and the mass spectrometer such that a conduit interior volume is contiguous with an interior volume of the GC oven; routing the GC column through the GC oven and conduit interior volume to an ion source of the mass spectrometer; providing a flow of temperature regulated air or gas between a fan or blower of the gas chromatograph and the conduit interior volume; introducing the sample into the GC column; controlling the temperature of the GC oven interior volume and the conduit interior volume so as to facilitate analyte separation within the GC column and transfer of the separated analytes to the mass spectrometer; and analyzing the separated analytes with the mass spectrometer.

CROSS REFERENCE TO RELATED APPLICATION

This application is a Divisional of and claims, under 35 U.S.C. §120,the benefit of the filing date of U.S. application for patent Ser. No.12/399,574, now U.S. Pat. No. 8,549,893, titled “System and Method for aGas Chromatograph to Mass Spectrometer Interface” which was filed onMar. 6, 2009 and which is hereby incorporated by reference herein in itsentirety.

FIELD OF THE INVENTION

This invention relates to a mass spectrometer apparatus and inparticular to a transfer system useful with a mass spectrometer and gaschromatograph.

BACKGROUND OF THE INVENTION

Mass spectrometers generally include an ion source disposed in a vacuumsystem for achieving analysis of chemical substances. In the powerfulanalytical technique known Gas Chromatography-Mass Spectrometry (GC-MS),volatile analytes from mixtures are first separated into individualcomponents in a gas chromatograph (GC) and the separated samples aredirectly transferred into a mass spectrometer (MS) for subsequent massanalysis. The GC has a tubular column which is heated (or possiblycooled) to a controlled temperature or along a controlled temperatureprofile in a gas chromatograph oven (GC oven).

For clean separation of analytes, the temperature of a GC column needsto be carefully controlled, often to within a fraction of a degree.Further, in order to increase throughput, the temperature is often notmaintained static during an entire separation, but is ramped along acontrolled temperature profile. A GC oven for these purposes usuallycomprises a thermally insulated housing internally accessible through adoor, a heating element, and a motor driven fan for stirring the air inthe housing. The stirring fan continuously mixes the air within the ovento minimize temperature gradients which could adversely affect theperformance of the chemical processes within the GC column. Variousbaffles or plenums are generally incorporated into the heatedcompartment of the GC oven in order to direct and control air flow. Tofacilitate rapid cooling or cool-down, a GC oven often typicallycomprises intake ports to allow air or gas to bleed into the oven andoutlet ports to exhaust hot air or gas from the oven. For use withhighly volatile compounds, the temperature of the GC oven may beaccurately controlled at low temperatures (slightly above or even belowambient) by feeding air or a cooled gas into the inlet ports.

The effluent from the GC column needs to be transferred from the GCcolumn, to the MS ion source that is held in vacuum. However, during thetransfer (performed conventionally by means of a transfer line), it isnecessary to maintain a uniform temperature across the length of thetransfer line. If a significant temperature gradient exists so that thetemperature varies at different points along the transfer line, coldspots may occur to cause condensation from the gas phase of the sampleso that it will either not be passed through to the MS or will exhibitexcessive chromatographic peak broadening or peak tailing. On the otherhand, hot spots that appear may cause some compounds to degradethermally with a resultant change in their chemical structure. Similareffects can occur even if the transfer line is at a uniform temperatureif the temperature of the transfer line is either too cold or too hotduring the elution of any given chemical compound. Additionally,excessive transfer line temperatures can lead to elevated “chemicalnoise” and lower signal-to-noise ratio for any given analytical results.

Prior art approaches for transferring column effluent to a massspectrometer have employed isothermal, independently heated transferlines comprising tubing situated between a gas chromatograph and a massspectrometer and through which the GC column is passed. As one example,FIG. 1A illustrates a first conventional system for interfacing a gaschromatograph 10 to a mass spectrometer 20. The gas chromatograph 10comprises a gas chromatograph oven having an insulated oven housing 19.The oven has a temperature controlled oven interior volume 18 containingat least a portion of GC column 12. The mass spectrometer 20 compriseshousing 29 that has an interior 28 containing ion source 22. The massspectrometer interior 28 is generally under vacuum during operation ofthe mass spectrometer. A portion of the GC column 12 passes through thefull length of the interior of a transfer tube 14 and into the ionsource 22. The GC column 12 is sealed to the transfer tube by vacuumfitting 13 and the transfer tube 14 is sealed to the mass spectrometer20 by seal 16. As in other conventional systems for interfacing a gaschromatograph to a mass spectrometer, a portion of the GC column 12resides within a section of the transfer tube 14 that is neither withinthe GC oven interior 18 nor the MS interior 28. The conventional systemshown in FIG. lA maintains this section at an appropriate temperature bymeans of a heating tape 11 wrapped around and in close thermal contactwith the transfer tube 14. Resistance heating produced by electricalcurrent supplied by electrical leads 15 elevates the temperature of theheating tape 11 and, consequently, of the sections of the transfer tubein contact with the heating tape and the GC column within the transfertube.

FIG. 1B illustrates a second conventional system for interfacing a gaschromatograph 10 to a mass spectrometer 20. In the system shown in FIG.1B, a separate box-like oven 17 that encloses a portion of the transfertube is used instead of heating tape. Power is supplied to the oven 17by electrical leads 15.

FIG. 1C illustrates a third conventional system for interfacing a gaschromatograph 10 to a mass spectrometer 20. The system shown in FIG. 1Ccomprises a transfer line 30 disposed between the gas chromatograph 10and the mass spectrometer 20 that includes two additional tubes—a middletube 32 and an outer tube 33—that enclose the transfer tube 14, whichcomprises an inner tube. The middle tube encloses, in addition to thetransfer tube, a temperature sensor (not shown) and a heater (not shown)that extends along the full length of the middle tube adjacent to theinner tube. The space between the middle tube 32 and the outer tube 33acts as insulation, thereby limiting heat transfer to the outer tube.This space may be under vacuum in order to provide thermal insulation,or may be packed with an insulative material such as glass or ceramicfibers.

These conventional approaches have experienced problems of eithercomplexity, increased difficulty of accessing the GC column,non-uniformity of heat distribution within the transfer line, ornon-matching of the transfer line temperature to the internaltemperature of the GC oven. Although it would be possible tocontrollably ramp the interface temperature in accordance with the GCoven profile, the thermal mass of such devices precludes convenient andrapid cooldown to the initial conditions necessary for subsequentanalysis. Further, using these conventional approaches, it is difficultto maintain a controlled temperature of the transfer line at nearambient conditions or at sub-ambient conditions.

SUMMARY OF THE INVENTION

In order to overcome the aforementioned problems associated with theconventional art, an improved gas chromatograph to mass spectrometerinterface is herein disclosed. The gas chromatograph to massspectrometer interface disclosed herein does not require any separatetemperature controller for a transfer line but, instead, uses heated airdirectly from a GC oven blower to thermally regulate a GC column,possibly contained within a low thermal mass section of tubing.

Accordingly, various embodiments according to a first aspect of theinvention may comprise a system for interfacing a gas chromatograph (GC)to a mass spectrometer, the GC comprising a GC column partiallycontained within a GC oven, the mass spectrometer comprising a housingenclosing an interior having an ion source, the system comprising: aconduit extending from the GC oven to the mass spectrometer andcomprising an interior volume that is contiguous and conterminous withan interior volume of the GC oven; and a duct extending from thevicinity of a blower of the GC oven to the conduit interior volume andoperable so as to transmit a flow of air or gas from the blower into theconduit interior volume, or to the blower from the conduit interiorvolume, wherein a portion of the GC column extends through the conduitinterior volume to the ion source.

Various embodiments according to another aspect of the invention maycomprise a method for interfacing a gas chromatograph (GC) to a massspectrometer, wherein the GC comprises a GC column partially containedwithin a GC oven and the mass spectrometer comprises a housing enclosingan interior having an ion source, the method comprising: providing aconduit extending from the GC oven to the mass spectrometer and havingan interior volume such that the conduit interior volume is contiguousand conterminous with an interior volume of the GC oven; providing aduct extending from the vicinity of a blower of the GC oven to theconduit interior volume so as to transmit a flow of air or gas to orfrom the blower into or out of the conduit interior volume; and routinga portion of the GC column through the conduit interior volume to theion source.

Various embodiments according to still another aspect of the inventionmay comprise a method of operating a gas chromatograph-mass spectrometer(GC-MS) comprising a gas chromatograph column (GC column) for separatinganalytes of a sample, a gas chromatograph oven (GC oven) and a massspectrometer, the method comprising: providing a conduit extendingbetween the GC oven and the mass spectrometer such that an interiorvolume of the conduit is contiguous and conterminous with an interiorvolume of the GC oven; routing the GC column through the GC oven andthrough the conduit interior volume to an ion source of the massspectrometer; providing a flow of air or gas to or from a blower of thegas chromatograph to the conduit interior volume; introducing the sampleinto the GC column; controlling the temperature of the interior volumeof the GC oven and the interior volume of the conduit using the air orgas so as to facilitate analyte separation within the GC column andtransfer of the separated analytes to the mass spectrometer; andanalyzing the separated analytes with the mass spectrometer.

BRIEF DESCRIPTION OF THE DRAWINGS

The above noted and various other aspects of the present invention willbecome apparent from the following description which is given by way ofexample only and with reference to the accompanying drawings, not drawnto scale, in which:

FIG. 1A is a schematic illustration of a first conventional system forinterfacing a gas chromatograph to mass spectrometer;

FIG. 1B is a schematic illustration of a second conventional system forinterfacing a gas chromatograph to mass spectrometer;

FIG. 1C is a schematic illustration of a third conventional system forinterfacing a gas chromatograph to mass spectrometer; and

FIG. 2A is a schematic illustration of a first gas chromatograph to massspectrometer interface in accordance with some embodiments of thepresent invention;

FIG. 2B is a schematic illustration of a second gas chromatograph tomass spectrometer interface in accordance with some embodiments of thepresent invention;

FIG. 3A is a schematic illustration of a gas chromatograph to massspectrometer interface partially contained within a GC oven inaccordance with some embodiments of the present invention;

FIG. 3B is a schematic illustration of another gas chromatograph to massspectrometer interface partially contained within a GC oven inaccordance with some embodiments of the present invention;

FIG. 3C is a schematic illustration of still another gas chromatographto mass spectrometer interface partially contained within a GC oven inaccordance with some embodiments of the present invention;

FIG. 3D is a schematic illustration of yet another gas chromatograph tomass spectrometer interface partially contained within a GC oven inaccordance with some embodiments of the present invention.

DETAILED DESCRIPTION

The following description is presented to enable any person skilled inthe art to make and use the invention, and is provided in the context ofa particular application and its requirements. Various modifications tothe described embodiments will be readily apparent to those skilled inthe art and the generic principles herein may be applied to otherembodiments. Thus, the present invention is not intended to be limitedto the embodiments and examples shown but is to be accorded the widestpossible scope in accordance with the features and principles shown anddescribed. The particular features and advantages of the invention willbecome more apparent with reference to the appended FIGS. 2-3, taken inconjunction with the following description.

FIG. 2A is a schematic illustration of a gas chromatograph to massspectrometer interface in accordance with the present invention. In FIG.2A, reference number 10 refers to a gas chromatograph (only a portion ofwhich is illustrated) and reference number 20 refers to a massspectrometer (only a portion of which is illustrated). The system 100shown in FIG. 2A comprises a conduit 40 which partially encloses aninterior volume 41 which is contiguous and conterminous with the heatedGC oven interior volume 18. The conduit 40 is sealed, in an air-tightfashion, to the housing 19 of the GC oven and extends outward from thehousing 19 and between the GC and the MS such that the conduit interiorvolume 41 comprises an outward extension of the interior volume 18 ofthe GC oven. This configuration enables the heated internal air or gasof the oven to flow into or out of the conduit interior volume 41. Theconduit 40 is preferably lined with a low thermal mass rigidized ceramicfiber insulation 52 in order to minimize thermal lag and heat loss tothe outer shell of the conduit 40. The use of rigidized insulationallows operation without heat loss to a metallic liner (such as istypically used in the lining of a GC oven) while at the same timeprevents erosion of the insulator as would occur for loose glass orceramic wool type insulation materials. As one example, the insulation52 may comprise the material HTP as is described in NASA Tech Briefs,Winter 1985, Vol. 4, MSC-20654.

A duct 42 in the system 100 (FIG. 2A) channels higher pressureoven-heated air from periphery of an oven blower or fan into the conduitinterior volume 41 such that flowing temperature regulated air or gas 46flows along and around the entire length of the transfer tube 14contained within the volume 41. This free flow of air around and alongthe transfer tube 14 allows thermal regulation of the section of the GCcolumn contained within the transfer tube within the conduit interiorvolume. Preferably, the end of the duct disposed within the conduitshould be placed such that the flowing temperature-regulated air or gasarrives or exits at or close to the end of the conduit 40 furthest fromthe GC oven. This ensures that no dead volume remains in the conduitwhich would otherwise result in a temperature gradient along its length.

The transfer tube 14 should be sufficiently rigid to support the columnbut should have sufficiently low thermal mass so as to enable oventemperature changes to be communicated to the section of column withinthe transfer tube with suitably low time lag. This enables thetemperature of the column within volume 41 to track the controlledtemperature of the oven interior 18 without resulting in adverse bandbroadening, peak tailing or sample decomposition. As one example, theinventors have discovered that 1.6 millimeter (mm) or 1/16 inch orsmaller outer diameter stainless steel tubing fulfills theserequirements. However, the tubing may have a larger diameter (up to 2mm) in order to accommodate the largest available diameter capillary GCcolumn. The transfer tube 14 is preferably terminated in the GC ovenproper in order to conveniently access vacuum fitting 13 for columninstallation and removal. Although the vacuum fitting 13 could bepositioned closely to ion source 22 in order to further reduce thermalmass, thus tracking overall oven temperature more accurately, it ispreferable that some degree of thermal mass near the terminal end of theGC column is present in order to offset potential peak splitting due tothe laminar air flow conditions in this area. The effects of peaksplitting caused by rapid GC temperature fluctuations are described inF. Munari and S. Trestianu “Thermal peak splitting in capillary gaschromatography” Journal of Chromatography, 279 (1983) 457-472.

The system shown in FIG. 2A extends accurate heating control of thecolumn to within close proximity to the mass spectrometer 20. As seen inthe example of FIG. 2A, the end of the conduit 40 may protrude past orbeyond the mass spectrometer housing 29 through a gap or aperture 49 inthe MS housing 29. The vacuum within the mass spectrometer may be sealedagainst ambient air intrusion by means, for instance, of a flange 48that is sealed, in vacuum-tight fashion by means of a gasket or O-ring50, against a wall or other structural feature of the MS housing.

Air or gas from within the GC oven is prevented from entering the massspectrometer and the integrity of the MS vacuum may be maintained (whilemaintaining proximity of the conduit interior volume 41 to the massspectrometer 20) by means of a membrane 44 through which thecolumn-containing transfer tube passes and which comprises an air-tightand vacuum tight seal over exit port 47 of the conduit 40. As oneexample, the membrane may comprise a stainless steel foil of thicknesswithin the range of approximately 0.010 to 0.020 inches. The diameterand thickness of the membrane 44 can be selected so as to offer minimalheat loss from oven air to the structural enclosure of conduit 40, whileat the same time offering sufficient strength to avoid a vacuum ruptureimposed by the high vacuum of the MS interior 28. Additionally, thismembrane allows sufficient heating of terminal end of transfer tube 14by ion source 22 without excessive heat loss from the ion source.

The conduit 40 may comprise an integral part of the GC oven housing 19.Alternatively, the conduit 40 may be provided as a modular accessorythat attaches to or mates with a pre-existing gap 9 in a wall of the GCoven. For instance, the gap 9 may comprise a pre-existing output port oraperture, such as, for instance, a port or aperture to which variousaccessory apparatuses (e.g., detectors) may be interchangeably mated orfitted.

FIG. 2B illustrates an embodiment, in accordance with the invention, inwhich a portion of the duct 42 is located within a portion (such as awall portion) of the GC oven housing 19. This configuration frees upspace within the interior of the GC oven for positioning a portion ofthe column. Further, the configuration shown in FIG. 2B may cause lessinterruption of the air or gas flow within the GC oven.

FIG. 3A is a schematic illustration of a gas chromatograph to massspectrometer interface 155 partially contained within a GC oven 7 andshowing one method of fluidic coupling between an inlet of the duct 42and a fan or blower 43 within the GC oven 7. As shown in FIG. 3A, theinlet of the duct 42 may be disposed behind a plenum or partition 51within the GC oven so as to intercept the radial flow of flowing gas 46emanating from the blower fan 43. Returning air or gas 45 is drawn intowards fan 43 and is channeled towards the central hub of the fan 43 byone or more gaps 55 of or within the plenum or partition 51. The gaps 55may comprise, for instance, perforations or slits within the plenum orpartition 51. In the configuration shown in FIG. 3A, air or gas set inmotion by fan 43 is forced to flow laterally outward in a region betweenthe plenum 51 and the GC oven housing 19 as a result of confinementbetween these latter two elements. Consequently, a pressure differentialis established with a relatively higher pressure region existinglaterally outward from the fan 43 between the plenum 51 and the GC ovenhousing 19. As shown in FIG. 3A, the inlet of the duct 42 is disposed soas to intercept a portion of the air or gas within this high pressureregion and direct it into the relatively lower pressure conduit interiorvolume 41. FIG. 3A illustrates an embodiment in which a portion of theduct 42 is contained within the GC oven housing 19 as shown in FIG. 2B.However, the configuration illustrated in FIG. 2A, configuration inwhich the duct is positioned within the GC oven interior, could also beused.

FIG. 3B is a schematic illustration of another gas chromatograph to massspectrometer interface 157 partially contained within a GC oven 7. Thesystem 157 shown in FIG. 3B is similar to the system 155 shown in FIG.3A, except that, in the system 157, a heater or heating element 53 ispositioned between the fan or blower 43 and the inlet of the duct 42. Inthis configuration, air or gas 46 is forced to flow adjacent to theheater 53 just prior to entering the duct 42. This configuration cancompensate for any heat losses along the length of the duct. AlthoughFIG. 3B illustrates a configuration in which a portion of the duct 42 iscontained within the GC oven housing 19 (i.e., as in FIG. 2B), theconfiguration in which the duct is positioned within the GC oveninterior (i.e., as in FIG. 2A) could also be used.

FIG. 3C is a schematic illustration of still another gas chromatographto mass spectrometer interface 159 partially contained within a GC oven7 and showing another method of fluidic coupling between an inlet of theduct 42 and the fan or blower 43. In the configuration shown in FIG. 3C,the inlet of the duct 42 is positioned within a relatively lowerpressure region near the gap (or gaps) 55 in the plenum or partition 51.In this situation, the duct draws returning air or gas 45 out of theconduit interior volume 41, causing temperature regulated air or gas toflow from the GC oven interior 18 into the conduit interior volume 41.Alternatively, any location within the GC oven confines offering apressure differential is suitable in order to establish flow within theduct 42. Although FIG. 3C illustrates a configuration in which a portionof the duct 42 is contained within the GC oven housing 19 (i.e., as inFIG. 2B), the configuration in which the duct is positioned within theGC oven interior (i.e., as in FIG. 2A) could also be used.

FIG. 3D illustrates is a schematic illustration of yet another gaschromatograph to mass spectrometer interface 161 partially containedwithin a GC oven 7. In the configuration illustrated in FIG. 3D, aportion of the duct 42 within the conduit 40 encloses a portion of thetransfer tube 14 such that the flowing temperature regulated air or gas46 is confined along the portion of the transfer tube 14, therebyimproving heat transfer from the air or gas 46 to the transfer tube.Although FIG. 3D illustrates a configuration in which a portion of theduct 42 is contained within the GC oven housing 19 (i.e., as in FIG.2B), the configuration in which the duct is positioned within the GCoven interior (i.e., as in FIG. 2A) could also be used.

The discussion included in this application is intended to serve as abasic description. Although the present invention has been described inaccordance with the various embodiments shown and described, one ofordinary skill in the art will readily recognize that there could bevariations to the embodiments and those variations would be within thespirit and scope of the present invention. The reader should be awarethat the specific discussion may not explicitly describe all embodimentspossible; many alternatives are implicit. Accordingly, manymodifications may be made by one of ordinary skill in the art withoutdeparting from the spirit, scope and essence of the invention. Neitherthe description nor the terminology is intended to limit the scope ofthe invention. Any publications, patents or patent applicationpublications mentioned in this specification are explicitly incorporatedby reference in their respective entirety.

What is claimed is:
 1. A method of operating a gas chromatograph-massspectrometer (GC-MS) comprising a gas chromatograph column (GC column)for separating analytes of a sample, a gas chromatograph oven (GC oven)and a mass spectrometer, the method comprising: providing a conduitextending between the GC oven and the mass spectrometer such that aninterior volume of the conduit is contiguous with an interior volume ofthe GC oven; routing the GC column through the GC oven and through theconduit interior volume to an ion source of the mass spectrometer;providing a flow of temperature regulated air or gas between a fan orblower of the gas chromatograph and the conduit interior volume using aduct extending from the vicinity of a blower of the GC oven to theconduit interior volume so as to transmit the flow of temperatureregulated air or gas between the blower and the conduit interior volume;introducing the sample into the GC column; controlling the temperatureof the interior volume of the GC oven and the interior volume of theconduit so as to facilitate analyte separation within the GC column andtransfer of the separated analytes to the mass spectrometer; andanalyzing the separated analytes with the mass spectrometer.
 2. Themethod of claim 1, wherein the step of providing a conduit extendingbetween the GC oven and the mass spectrometer includes situating theconduit such that a portion of the conduit protrudes through a port oraperture in the mass spectrometer housing.
 3. The method of claim 1,wherein the step of providing a conduit extending between the GC ovenand the mass spectrometer includes situating the conduit such that theconduit mates with a port or aperture of the GC oven.
 4. The method ofclaim 1, wherein the step of routing the GC column through the GC ovenand through the conduit interior volume to an ion source of the massspectrometer includes the steps of: providing a transfer tube within theconduit interior volume; and routing at least a portion of the GC columnthrough the transfer tube.
 5. The method of claim 1, wherein the step ofproviding a flow of temperature regulated air or gas between a fan orblower of the gas chromatograph and the conduit interior volumecomprises: providing a circulating flow of the temperature regulated airor gas comprising a first circulation portion that is outside of anddirected away from the GC oven interior volume and a second returningcirculation portion outside of and directed towards the GC oven interiorvolume, wherein one of the first and second circulation portions iswithin the duct and the other one of the circulation portions is withinthe conduit.